依他尼酸对猴眼房水流出动力学的影响。

Croft M A, Hubbard W C, Kaufman P L

Department of Ophthalmology and Visual Sciences, University of Wisconsin Medical School, Madison.

Invest Ophthalmol Vis Sci. 1994 Mar;35(3):1167-75.

PURPOSE

To determine the long-term effect of ethacrynic acid (ECA) on aqueous outflow dynamics in ocular normotensive monkeys.

METHODS

(1) Twelve cynomolgus monkeys received 10 microliters of 2.5 mM (= 7.5 micrograms) ECA intracamerally in one eye, vehicle in the other; outflow facility (perfusion) was determined at 1 hour, 24 hours, or 1 week, and intraocular pressure (IOP; applanation) at 24 hours, 1 week, and 6 to 7 weeks later. Six other cynomolgi received 10 microliters of 0.13 or 1.3 mM phalloidin in one eye 45 minutes before receiving ECA OU; facility was measured 1 hour after ECA. (2) Groups of five rhesus monkeys underwent intracameral injection of 2.5, 5.0, or 10 micrograms ECA in one eye, vehicle in the other, with IOP measured hours to weeks thereafter. (3) Five rhesus monkeys received 540 micrograms of ECA unilaterally as a 30-microliter topical drop once daily for 4 days. On the first and fourth treatment days, baseline IOP, pupil diameter, and refraction were measured immediately before and again at 2, 4, and 7 hours after topical treatment.

RESULTS

(1) ECA divided by vehicle facility averaged 1.83 +/- 0.23 (SEM) (P < 0.02, n = 6), 1.50 +/- 0.27 (P < 0.11, n = 7), and 1.05 +/- 0.10 (n = 7) at 1 hour, 24 hours, and 1 week, respectively. IOP was 1 to 2 mm Hg lower in ECA eyes 24 hours (P < 0.05, n = 5) and 6 to 7 weeks (P < 0.05, n = 7) after treatment. Phalloidin did not diminish the 1-hour ECA facility effect. (2) Five (but not 2.5 or 10) micrograms of ECA lowered IOP 1 to 3 mm Hg, starting at 2 hours and lasting up to 48 hours. The maximum ECA effect (-2.6 +/- 0.25 mm Hg; P < 0.001, n = 5) occurred at 4 hours. IOP, corneal thickness and endothelial cell count, and anterior chamber depth were not significantly different 8 weeks after 5 micrograms ECA or vehicle. (3) Once-daily unilateral topical application of 540 micrograms of ECA induced no change in IOP, refraction, or pupil diameter compared to contralateral vehicle-treated control eyes. There were no significant ECA-related ocular bio-microscopic abnormalities.

CONCLUSIONS

ECA may lower IOP and increase outflow facility longer than previously thought, but not by affecting meshwork actin filaments.

目的

确定依他尼酸（ECA）对眼压正常的猴眼房水流出动力学的长期影响。

方法

（1）12只食蟹猴一只眼经前房内注射10微升2.5 mM（=7.5微克）ECA，另一只眼注射赋形剂；在1小时、24小时或1周时测定流出易度（灌注法），并在24小时、1周以及6至7周后测定眼压（压平眼压计测量）。另外6只食蟹猴在双眼接受ECA前45分钟，一只眼注射10微升0.13或1.3 mM鬼笔环肽；在注射ECA 1小时后测量流出易度。（2）将5只恒河猴分为一组，一只眼经前房内注射2.5、5.0或10微克ECA，另一只眼注射赋形剂，之后数小时至数周内测量眼压。（3）5只恒河猴每天一次单侧局部滴注540微克ECA，共4天，每次30微升。在首次和第四次治疗日，在局部治疗前及治疗后2、4和7小时立即测量基线眼压、瞳孔直径和屈光。

结果

（1）ECA与赋形剂流出易度之比在1小时、24小时和1周时分别平均为1.83±0.23（SEM）（P<0.02，n = 6）、1.50±0.27（P<0.11，n = 7）和1.05±0.10（n = 7）。治疗后24小时（P<0.05，n = 5）和6至7周（P<0.05，n = 7），ECA处理眼的眼压降低1至2 mmHg。鬼笔环肽未减弱ECA在1小时时对流出易度的作用。（2）5微克（而非2.5或10微克）ECA可使眼压降低1至3 mmHg，从2小时开始，持续长达48小时。ECA的最大作用（-2.6±0.25 mmHg；P<0.001，n = 5）出现在4小时。5微克ECA或赋形剂处理8周后，眼压、角膜厚度和内皮细胞计数以及前房深度无显著差异。（3）与对侧用赋形剂处理的对照眼相比，每天一次单侧局部应用540微克ECA未引起眼压、屈光或瞳孔直径的变化。未发现与ECA相关的明显眼生物显微镜异常。